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42 ■ The Developing Human
3
Formation of the Bilaminar
Embryonic Disc: Second Week
42
Completion of Implantation and Continuation of Embryonic
Development
43
Formation of the Amniotic Cavity, Embryonic Disc,
and Umbilical Vesicle
44
Development of the Chorionic Sac
45
Implantation Sites of Blastocysts
45
Summary of Implantation
48
Summary of the Second Week
51
Clinically Oriented Problems
53
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Formation of the Bilaminar Embryonic Disc: Second Week ■ 43
Implantation of the blastocyst is completed during the
second week. As this process occurs, morphologic changes
in the embryoblast produce a bilaminar embryonic disc
composed of epiblast and hypoblast (Fig. 3-1A). The
embryonic disc gives rise to the germ layers that form all
the tissues and organs of the embryo. Extraembryonic
structures forming during the second week are the
amniotic cavity, amnion, umbilical vesicle (yolk sac),
connecting stalk, and chorionic sac.
Uterine gland
Endometrial capillary
Syncytiotrophoblast
COMPLETION OF IMPLANTATION AND
CONTINUATION OF EMBRYONIC DEVELOPMENT
Implantation of the blastocyst is completed by the end of
the second week. It occurs during a restricted time period
6 to 10 days after ovulation. As the blastocyst implants (see
Fig. 3-1), more trophoblast contacts the endometrium and
differentiates into
● The cytotrophoblast, a layer of cells that is mitotically
active and forms new cells that migrate into the
increasing mass of syncytiotrophoblast, where they
fuse and lose their cell membranes
● The syncytiotrophoblast, a rapidly expanding, multinucleated mass in which no cell boundaries are
discernible
The erosive syncytiotrophoblast invades the endometrial connective tissue, and the blastocyst slowly embeds
itself in the endometrium. Syncytiotrophoblastic cells
displace endometrial cells at the implantation site. The
endometrial cells undergo apoptosis (programmed cell
death), which facilitates the invasion. The molecular
mechanisms of implantation involve synchronization
between the invading blastocyst and a receptive endometrium. The microvilli of endometrial cells (pinopodes),
cell adhesion molecules, cytokines, prostaglandins,
homeobox genes, growth factors, and matrix metalloproteins play a role in making the endometrium receptive.
The connective tissue cells around the implantation site
accumulate glycogen and lipids and assume a polyhedral
appearance. Some of these cells—decidual cells—
degenerate adjacent to the penetrating syncytiotrophoblast. The syncytiotrophoblast engulfs these degenerating
cells, providing a rich source of embryonic nutrition.
The syncytiotrophoblast produces a hormone—human
chorionic gonadotrophin (hCG), which enters the maternal
blood via lacunae (Latin, hollow cavities) in the syncytiotrophoblast (see Fig. 3-1C). hCG maintains the hormonal
activity of the corpus luteum in the ovary during preg-
Amnion
Amniotic
cavity
Epiblast
A
Exocoelomic
cavity
Exocoelomic
membrane
Endometrial
epithelium
Cytotrophoblast
Hypoblast
Syncytiotrophoblast
Amnion
Bilaminar
embryonic
disc
Exocoelomic membrane
Exocoelomic cavity
B
Cytotrophoblast
Amnion
Uterine
gland
Maternal
blood in
lacunae
FIGURE 3-1. Implantation of a blastocyst in the endometrium. The
actual size of the conceptus is 0.1 mm, approximately the size of
the period at the end of this sentence. A, Drawing of a section
through a blastocyst partially implanted in the endometrium
(approximately 8 days). Note the slitlike amniotic cavity. B, An
enlarged three-dimensional sketch of a slightly older blastocyst
after removal from the endometrium. Note the extensive
syncytiotrophoblast at the embryonic pole (side of the blastocyst
containing the embryonic disc). C, Drawing of a section through a
blastocyst of approximately 9 days implanted in the endometrium.
Note the lacunae appearing in the syncytiotrophoblast. The term
yolk sac is a misnomer because it contains no yolk.
Bilaminar
embryonic
disc
C
Primary
umbilical
vesicle
(yolk sac)
Extraembryonic
mesoderm
Endometrial epithelium
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44 ■ The Developing Human
nancy. The corpus luteum is an endocrine glandular structure that secretes estrogen and progesterone to maintain
the pregnancy. Highly sensitive radioimmunoassays are
available for detecting hCG and pregnancy and forms
the basis for pregnancy tests. Enough hCG is produced by
the syncytiotrophoblast at the end of the second week to
give a positive pregnancy test, even though the woman is
probably unaware that she is pregnant.
Amnion Syncytiotrophoblast
Endometrial
capillary
Lacunar
network
FORMATION OF THE AMNIOTIC CAVITY,
EMBRYONIC DISC, AND UMBILICAL VESICLE
As implantation of the blastocyst progresses, a small space
appears in the embryoblast. This space is the primordium
of the amniotic cavity (see Fig. 3-1A). Soon amniogenic
(amnion-forming) cells—amnioblasts—separate from the
epiblast and form the amnion, which encloses the
amniotic cavity (see Fig. 3-1B and C). Concurrently,
morphologic changes occur in the embryoblast that result
in the formation of a flat, almost circular bilaminar plate
of cells, the embryonic disc, consisting of two layers
(Fig. 3-2A):
● Epiblast, the thicker layer, consisting of high columnar
cells related to the amniotic cavity
● Hypoblast, consisting of small cuboidal cells adjacent
to the exocoelomic cavity
The epiblast forms the floor of the amniotic cavity and
is continuous peripherally with the amnion. The hypoblast
forms the roof of the exocoelomic cavity and is continuous with the thin exocoelomic membrane (see Fig. 3-1B).
This membrane, together with the hypoblast, lines the
primary umbilical vesicle. The embryonic disc now lies
between the amniotic cavity and the umbilical vesicle (see
Fig. 3-1C). Cells from the vesicle endoderm form a layer
of connective tissue, the extraembryonic mesoderm (see
Fig. 3-2A), which surrounds the amnion and umbilical
vesicle. This mesoderm continues to form from cells
that arise from the primitive streak (see Fig. 4-3). The
umbilical vesicle and amniotic cavities make morphogenetic movements of the cells of the embryonic disc
possible.
As the amnion, embryonic disc, and primary umbilical
vesicle form, isolated cavities— lacunae—appear in the
syncytiotrophoblast (see Figs. 3-1C and 3-2). The lacunae
soon become filled with a mixture of maternal blood from
ruptured endometrial capillaries and cellular debris from
eroded uterine glands. The fluid in the lacunar spaces—
embryotroph (Greek, trophe, nourishment)—passes to the
embryonic disc by diffusion and provides nutritive
material to the embryo.
The communication of the eroded endometrial capillaries with the lacunae establishes the primordial uteroplacental circulation. When maternal blood flows into
the lacunae, oxygen and nutritive substances are available
to the embryo. Oxygenated blood passes into the lacunae
from the spiral endometrial arteries, and poorly oxygenated
blood is removed from them through the endometrial veins.
The 10-day human conceptus (embryo and extraembryonic
membranes) is completely embedded in the endometrium (see
Fig. 3-2A). For approximately 2 days, there is a defect in
Epiblast
Cytotrophoblast
A
Primary
umbilical
vesicle
Closing
plug
Hypoblast
Extraembryonic
mesoderm
Actual size of implanted blastocyst :
Eroded
gland
Maternal
blood
Lacunar
network
•
Amniotic
cavity
Uterine gland
Extraembryonic
coelomic space
Extraembryonic
endodermal
lining of
umbilical
vesicle
(yolk sac)
Embryonic disc
B
Cytotrophoblast
FIGURE 3-2. Implanted blastocysts. A, At 10 days; B, at 12 days.
This stage of development is characterized by communication of the
blood-filled lacunar networks. Note in B that coelomic spaces have
appeared in the extraembryonic mesoderm, forming the beginning of
the extraembryonic coelom.
the endometrial epithelium that is filled by a closing plug,
a fibrinous coagulum of blood. By day 12, an almost
completely regenerated uterine epithelium covers the
closing plug (see Fig. 3-2B). As the conceptus implants, the
endometrial connective tissue cells undergo a transformation, the decidual reaction. After the cells swell because
of the accumulation of glycogen and lipid in their
cytoplasm, they are known as decidual cells. The primary
function of the decidual reaction is to provide nutrition for
the early embryo and an immunologically privileged site
for the conceptus.
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Formation of the Bilaminar Embryonic Disc: Second Week ■ 45
FIGURE 3-3. Photograph of the endometrial surface of the uterus,
showing the implantation site of the 12-day embryo shown in Figure
3-4. The implanted conceptus produces a small elevation (arrow)
(×8). (From Hertig AT, Rock J: Contrib Embryol Carnegie Inst 29:127,
1941. Courtesy of the Carnegie Institution of Washington.)
In a 12-day embryo, adjacent syncytiotrophoblastic
lacunae have fused to form lacunar networks (see
Fig. 3-2B), giving the syncytiotrophoblast a spongelike
appearance. The lacunar networks, particularly obvious
around the embryonic pole, are the primordia of the
intervillous spaces of the placenta (see Chapter 7). The
endometrial capillaries around the implanted embryo
become congested and dilated to form sinusoids, thinwalled terminal vessels that are larger than ordinary capillaries. The syncytiotrophoblast erodes the sinusoids, and
maternal blood flows freely into the lacunar networks.
The trophoblast absorbs nutritive fluid from the lacunar
networks, which is transferred to the embryo. Growth of
the bilaminar embryonic disc is slow compared with
growth of the trophoblast (see Figs. 3-1 and 3-2). The
implanted 12-day embryo produces a minute elevation on
the endometrial surface that protrudes into the uterine
lumen (Figs. 3-3 and 3-4).
As changes occur in the trophoblast and endometrium,
the extraembryonic mesoderm increases and isolated
extraembryonic coelomic spaces appear within it
(see Figs. 3-2 and 3-4). These spaces rapidly fuse to form
a large isolated cavity, the extraembryonic coelom
(Fig. 3-5A). This fluid-filled cavity surrounds the amnion
and umbilical vesicle, except where they are attached to the
chorion by the connecting stalk. As the extraembryonic
coelom forms, the primary umbilical vesicle decreases in
size and a smaller secondary umbilical vesicle forms (see
Fig. 3-5B). This smaller vesicle is formed by extraembryonic endodermal cells that migrate from the hypoblast
inside the primary umbilical vesicle (Fig. 3-6). During
formation of the secondary umbilical vesicle, a large
part of the primary umbilical vesicle is pinched off (see
Fig. 3-5B). The umbilical vesicle contains no yolk; however,
it has important functions (e.g., it is the site of origin of
primordial germ cells [see Chapter 12]). It may have a role in
the selective transfer of nutrients to the embryo.
DEVELOPMENT OF THE CHORIONIC SAC
The end of the second week is characterized by the
appearance of primary chorionic villi (Figs. 3-5 and 3-7).
Proliferation of cytotrophoblastic cells produces cellular
extensions that grow into the syncytiotrophoblast. The
growth of these extensions is thought to be induced by
the underlying extraembryonic somatic mesoderm. The
cellular projections form primary chorionic villi, the first
stage in the development of the chorionic villi of the
placenta.
The extraembryonic coelom splits the extraembryonic
mesoderm into two layers (see Fig. 3-5A and B):
● Extraembryonic
somatic mesoderm, lining the
trophoblast and covering the amnion
● Extraembryonic splanchnic mesoderm, surrounding
the umbilical vesicle
The extraembryonic somatic mesoderm and the two
layers of trophoblast form the chorion (see Fig. 3-7B).
The chorion forms the wall of the chorionic sac, within which
the embryo and its amniotic sac and umbilical vesicle are
suspended by the connecting stalk. The extraembryonic
coelom is now called the chorionic cavity. The amniotic
sac and the umbilical vesicle can be thought of as two
balloons pressed together (at the site of embryonic disc)
and suspended by a cord (connecting stalk) from the inside
of a larger balloon (chorionic sac). Transvaginal ultrasonography (endovaginal sonography) is used for measuring
the chorionic (gestational) sac diameter (Fig. 3-8). This
measurement is valuable for evaluating early embryonic
development and pregnancy outcome.
The 14-day embryo still has the form of a flat
bilaminar embryonic disc (see Fig. 3-9), but the hypoblastic cells in a localized area are now columnar and form
a thickened circular area—the prechordal plate (see
Fig. 3-5B and C), which indicates the future site of the
mouth and an important organizer of the head region.
IMPLANTATION SITES OF BLASTOCYSTS
Implantation of blastocysts usually occurs in the
endometrium of the uterus, superior in the body of the
uterus, slightly more often on the posterior than on the
anterior wall. Implantation of a blastocyst can be detected
by ultrasonography and highly sensitive radioimmunoassays of hCG as early as the end of the second week.
EXTRAUTERINE IMPLANTATION
Blastocysts may implant outside the uterus. These
implantations result in ectopic pregnancies; 95% to
98% of ectopic implantations occur in the uterine
tubes, most often in the ampulla and isthmus
(Figs. 3-10 to 3-12). The incidence of ectopic
pregnancy has increased in most countries, ranging
from 1 in 80 to 1 in 250 pregnancies, depending on
the socioeconomic level of the population. In the
United States, the frequency of ectopic pregnancy is
approximately 2% of all pregnancies, and it is the main
cause of maternal deaths during the first trimester.
A woman with a tubal pregnancy has signs and
symptoms of pregnancy (e.g., misses her menstrual
period). She may also experience abdominal pain
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46 ■ The Developing Human
Spongy layer
Endometrial
glands
Endometrial
blood vessels
Compact layer
Endometrial
epithelium
Embryonic disc
A
Closing plug
Embryonic
epiblast
Embryonic
hypoblast
Amnion
Lacunar
network
Cytotrophoblast
Extraembryonic
coelom
B
and tenderness because of distention of the uterine
tube, abnormal bleeding, and irritation of the pelvic
peritoneum (peritonitis). The pain may be confused
with appendicitis if the pregnancy is in the right
uterine tube. Ectopic pregnancies produce β-human
chorionic gonadotropin at a slower rate than normal
pregnancies; consequently β-human chorionic
gonadotropin assays may give false-negative results
if performed too early. Transvaginal ultrasonography
is very helpful in the early detection of ectopic tubal
pregnancies.
There are several causes of tubal pregnancy, but
they are often related to factors that delay or prevent
SyncytioFIGURE 3-4. Implanted blastocyst.
trophoblast A, Section through the implantation
site of the 12-day embryo described
in Figure 3-3. The embryo is
Primary
embedded superficially in the
compact layer of the endometrium
umbilical
(×30). B, Higher magnification of the
vesicle
conceptus and surrounding
(yolk sac)
endometrium (×100). Lacunae
containing maternal blood are visible
in the syncytiotrophoblast. (From
ExtraHertig AT, Rock J: Contrib Embryol
embryonic Carnegie Inst 29:127, 1941.
mesoderm Courtesy of the Carnegie Institution of
Washington.)
transport of the cleaving zygote to the uterus, for
example, by mucosal adhesions in the uterine tube
or from blockage of it that is caused by scarring
resulting from pelvic inflammatory disease. Ectopic
tubal pregnancies usually result in rupture of the
uterine tube and hemorrhage into the peritoneal
cavity during the first 8 weeks, followed by death of
the embryo. Tubal rupture and hemorrhage
constitute a threat to the mother’s life. The affected
tube and conceptus are usually surgically removed
(see Fig. 3-12).
When blastocysts implant in the isthmus of the
uterine tube (see Fig. 3-11D), the tube tends to
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Formation of the Bilaminar Embryonic Disc: Second Week ■ 47
Extraembryonic
Maternal
somatic mesoderm sinusoid
Lacunar
network
Primary chorionic villus
Endometrium
Chorion
Extraembryonic
splanchnic mesoderm
A
Extraembryonic
coelom
Maternal blood
Primary
umbilical
vesicle
(yolk sac)
Primary chorionic villus
Connecting
stalk
Secondary
umbilical
vesicle
(yolk sac)
Prechordal
plate
B
Amnion
Remnant
of primary
umbilical
vesicle
Epiblast
Endometrial
epithelium
rupture early because this narrow part of the tube is
relatively unexpandable, and often with extensive
bleeding, probably because of the rich anastomoses
between ovarian and uterine vessels in this area.
When blastocysts implant in the uterine (intramural)
part of the tube (see Fig. 3-11E), they may develop
beyond 8 weeks before expulsion occurs. When a
uterine tubal pregnancy ruptures, it usually bleeds
profusely.
Blastocysts that implant in the ampulla or on
fimbriae of the uterine tube may be expelled into the
peritoneal cavity where they commonly implant in the
rectouterine pouch. In exceptional cases, an
abdominal pregnancy may continue to full term and
the fetus may be delivered alive through an
abdominal incision. Usually, however, the placenta
attaches to abdominal organs (Fig. 3-11G) and
causes considerable intraperitoneal bleeding.
Abdominal pregnancy increases the risk of maternal
death from hemorrhage by a factor of 90 when
compared with intrauterine pregnancy, and seven
times more than that for tubal pregnancy. In very
unusual cases, an abdominal conceptus dies and is
not detected; the fetus becomes calcified, forming a
“stone fetus”—lithopedion (Greek, lithos, stone,
+ paidion, child).
Simultaneous intrauterine and extrauterine
pregnancies are unusual, occurring approximately
1 in 7000. The ectopic pregnancy is masked initially
by the presence of the uterine pregnancy. Usually
the ectopic pregnancy can be terminated by surgical
removal of the involved uterine tube without
interfering with the intrauterine pregnancy (see
Fig. 3-12). Cervical implantations are unusual (see
Fig. 3-11); in some cases, the placenta becomes
firmly attached to fibrous and muscular tissues of
the cervix, often resulting in bleeding and requiring
subsequent surgical intervention, such as
hysterectomy (excision of uterus).
Extraembryonic
somatic mesoderm
Hypoblast
FIGURE 3-5. Drawings of sections through implanted human
Bilaminar
embryonic
disc
Prechordal plate
C
embryos, based mainly on Hertig and colleagues (1956). Observe
that (1) the defect in the endometrial epithelium has disappeared;
(2) a small secondary umbilical vesicle has formed; (3) a large cavity,
the extraembryonic coelom, now surrounds the umbilical vesicle and
amnion, except where the amnion is attached to the chorion by the
connecting stalk; and (4) the extraembryonic coelom splits the
extraembryonic mesoderm into two layers: extraembryonic somatic
mesoderm lining the trophoblast and covering the amnion and the
extraembryonic splanchnic mesoderm around the umbilical vesicle.
A, At 13 days, illustrating the decrease in relative size of the primary
umbilical vesicle and the early appearance of primary chorionic villi.
B, At 14 days, showing the newly formed secondary umbilical vesicle
and the location of the prechordal plate in its roof. C, Detail of the
prechordal plate outlined in B.
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48 ■ The Developing Human
Ectoderm of
amnion
Extraembryonic
mesoderm
Embryonic
ectoderm
Epiblast
Embryonic
mesoderm
Primitive streak
(see Chapter 4)
Notochordal
process
Bilaminar
embryonic
disc
Embryonic
endoderm
Endoderm of
umbilical vesicle
Extraembryonic
mesoderm
Hypoblast
FIGURE 3-6. Origin of embryonic tissues. The colors in the boxes are used in drawings of sections of conceptuses.
SUMMARY OF IMPLANTATION
Implantation of the blastocyst begins at the end of the
first week and is completed by the end of the second week.
The cellular and molecular events relating to implantation
are complex. It involves a receptive endometrium and
hormonal factors, such as estrogen, progesterone, prolactin, as well as cell adhesion molecules, growth factors,
and HOX genes, Implantation may be summarized as
follows:
● The zona pellucida degenerates (day 5). Its disappearance results from enlargement of the blastocyst and
degeneration caused by enzymatic lysis. The lytic
enzymes are released from the acrosomes of the
sperms that surround and partially penetrate the zona
pellucida.
● The blastocyst adheres to the endometrial epithelium
(day 6).
● The trophoblast differentiates into two layers: the
syncytiotrophoblast and cytotrophoblast (day 7).
● The syncytiotrophoblast erodes endometrial tissues,
and the blastocyst starts to embed in the endometrium (day 8).
● Blood-filled lacunae appear in the syncytiotrophoblast
(day 9).
● The
blastocyst sinks beneath the endometrial
epithelium, and the defect is filled by a closing plug
(day 10).
●
●
●
●
Lacunar networks form by fusion of adjacent lacunae
(days 10 and 11).
The syncytiotrophoblast erodes endometrial blood
vessels, allowing maternal blood to seep in and out of
lacunar networks, thereby establishing a uteroplacental circulation (days 11 and 12).
The defect in the endometrial epithelium is repaired
(days 12 and 13).
Primary chorionic villi develop (days 13 and 14).
PLACENTA PREVIA
Implantation of a blastocyst in the inferior segment
of the uterus near the internal os results in placenta
previa, a placenta that partially or completely covers
the os (see Fig. 3-11). Placenta previa may cause
bleeding because of premature separation of the
placenta during pregnancy or at delivery of the fetus
(see Chapter 7).
SPONTANEOUS ABORTION
OF
EMBRYOS
Most spontaneous abortions of embryos occur
during the first 3 weeks. Sporadic and recurrent
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Formation of the Bilaminar Embryonic Disc: Second Week ■ 49
Maternal blood
Trophoblastic
lacunar network
Primary chorionic villus
Syncytiotrophoblast
Extraembryonic
somatic mesoderm
Cytotrophoblastic core
Chorionic sac
Embryo
Chorionic cavity
A
B
C
FIGURE 3-7. A, Detail of the section (outlined in B) of the wall of the chorionic sac. B, Sketch of a 14-day conceptus illustrating the chorionic
sac and the shaggy appearance of it created by the primary chorionic villi. C, Drawing of a transverse section through a primary chorionic villus.
FIGURE 3-8. Endovaginal sonogram of an early chorionic (gestational)
sac. The mean gestational sac diameter is determined by adding the
three orthogonal dimensions (length, depth, and width) and dividing
by 3. (From Laing FC, Frates MC: Ultrasound evaluation during the
first trimester of pregnancy. In Callen PW [ed]: Ultrasonography in
Obstetrics and Gynecology, 4th ed. Philadelphia, WB Saunders,
2000.)
spontaneous abortions are two of the most common
gynecologic problems. The frequency of early
abortions is difficult to establish because they often
occur before a woman is aware that she is pregnant.
An abortion occurring several days after the first
missed period is very likely to be mistaken for a
delayed menstruation. Detection of a conceptus in
the menses (menstrual blood) is very difficult
because of its small size.
Study of most early spontaneous abortions
resulting from medical problems reveals abnormal
conceptuses. More than 50% of all known
spontaneous abortions result from chromosomal
abnormalities. The higher incidence of early
abortions in older women probably results from the
increasing frequency of nondisjunction during
oogenesis (see Chapter 2). It has been estimated
that from 30% to 50% of all zygotes never develop
into blastocysts and implant. Failure of blastocysts
to implant may result from a poorly developed
endometrium; however, in many cases, there are
probably lethal chromosomal abnormalities in the
embryo. There is a higher incidence of spontaneous
abortion of fetuses with neural tube defects, cleft
lip, and cleft palate.
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50 ■ The Developing Human
Decidua basalis
Lacunar network
Maternal blood
Connecting stalk
and amnion
Embryonic disc
Umbilical vesicle
(yolk sac)
Extraembryonic
coelom
Chorion and
chorionic villi
Endometrial
epithelium
A
Lacunar network
containing maternal blood
Trophoblast
Connecting stalk
Amniotic cavity
Amnion
Epiblast
Hypoblast
Secondary
umbilical vesicle
Bilaminar
embryonic
disc
Wall of umbilical vesicle
Extraembryonic coelom
(primordium of
chorionic cavity)
B
FIGURE 3-9. Photomicrographs of longitudinal sections of an implanted embryo at Carnegie stage 6, approximately 14 days. Note the large size
of the extraembryonic coelom. A, Low-power view (×18). B, High-power view (×95). The embryo is represented by the bilaminar embryonic disc
composed of epiblast and hypoblast. (From Nishimura H [ed]: Atlas of Human Prenatal Histology. Tokyo, Igaku-Shoin, 1983.)
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Formation of the Bilaminar Embryonic Disc: Second Week ■ 51
Embryo and
extraembryonic
membranes
Isthmus
Site of ectopic
tubal pregnancy
Ampulla
A
B
FIGURE 3-10. A, Frontal section of the uterus and left uterine tube, illustrating an ectopic pregnancy in the ampulla of the tube. B, Ectopic tubal
pregnancy. This axial sonogram through the left adnexa (placenta and extraembryonic membranes) of a 6-week pregnant patient shows a small
chorionic or gestational sac (arrow) in the left uterine tube with prominent vascularity in its periphery. This is characteristic of an ectopic tubal
pregnancy. The incidence of tubal pregnancy ranges from 1 in 80 to 1 in 250 pregnancies. Most ectopic implantations (95% to 97%) occur in
the uterine tube, usually in the isthmus or ampulla. (Courtesy of E.A. Lyons, MD, Professor of Radiology and Obstetrics and Gynecology, Health
Sciences Centre, University of Manitoba, Winnipeg, Manitoba, Canada.)
INHIBITION
OF IMPLANTATION
The administration of relatively large doses of
progestins and/or estrogens (“morning-after pills”)
for several days, beginning shortly after unprotected
sexual intercourse, usually does not prevent
fertilization but often prevents implantation of the
blastocyst. A high dose of diethylstilbestrol, given
daily for 5 to 6 days, may also accelerate passage of
the cleaving zygote along the uterine tube. Normally,
the endometrium progresses to the secretory phase
of the menstrual cycle as the zygote forms,
undergoes cleavage, and enters the uterus. The large
amount of estrogen disturbs the normal balance
between estrogen and progesterone that is necessary
for preparation of the endometrium for implantation.
An intrauterine device inserted into the uterus
through the vagina and cervix usually interferes with
implantation by causing a local inflammatory
reaction. Some intrauterine devices contain
progesterone that is slowly released and interferes
with the development of the endometrium so that
implantation does not usually occur.
SUMMARY OF THE SECOND WEEK
●
●
●
●
●
●
●
Rapid proliferation and differentiation of the trophoblast occurs as the blastocyst completes its implantation in the endometrium.
The endometrial changes resulting from the adaptation of these tissues in preparation for implantation
are known as the decidual reaction.
Concurrently, the primary umbilical vesicle (yolk sac)
forms and extraembryonic mesoderm develops. The
extraembryonic coelom forms from spaces that
develop in the extraembryonic mesoderm. The
coelom later becomes the chorionic cavity.
The primary umbilical vesicle becomes smaller and
gradually disappears as the secondary umbilical
vesicle develops.
The amniotic cavity appears as a space between the
cytotrophoblast and the embryoblast.
The embryoblast differentiates into a bilaminar embryonic disc consisting of epiblast, related to the
amniotic cavity, and hypoblast, adjacent to the
blastocyst cavity.
The prechordal plate develops as a localized
thickening of the hypoblast, which indicates the future
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52 ■ The Developing Human
Intestine
G
D
C
E
Mesentery
B
X
A
H
Ovary
F
Implantation at
internal os
Cervical implantation
FIGURE 3-11. Implantation sites of blastocysts. The usual site in the posterior wall of the uterus is indicated by an X. The approximate order of
frequency of ectopic implantations is indicated alphabetically (A, most common, H, least common). A to F, tubal pregnancies; G, abdominal
pregnancy; H, ovarian pregnancy. Tubal pregnancies are the most common type of ectopic pregnancy. Although appropriately included with
uterine pregnancy sites, a cervical pregnancy is often considered to be an ectopic pregnancy.
Uterine tube
Chorionic sac
A
B
Embryo
FIGURE 3-12. A tubal pregnancy. A, The uterine tube has been surgically removed and sectioned to show the conceptus implanted in the
mucous membrane (×3). B, Enlarged photograph of the normal-appearing 4-week embryo (×13). (Courtesy of Professor Jean Hay [retired],
Department of Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada.)
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Formation of the Bilaminar Embryonic Disc: Second Week ■ 53
cranial region of the embryo and the future site of the
mouth; the prechordal plate is also an important
organizer of the head region.
CLINICALLY ORIENTED PROBLEMS
• What would the physician likely tell her?
• Can women over 40 have normal babies?
• What tests and diagnostic techniques would likely
be performed?
Discussion of these problems appears at the back of the
book.
CASE 3-1
A 22-year-old woman who complained of a severe
“chest cold” was sent for a radiograph of her thorax.
• Is it advisable to examine a healthy female’s chest
radiographically during the last week of her
menstrual cycle?
• Are birth defects likely to develop in her conceptus
if she happens to be pregnant?
CASE 3-2
A woman who was sexually assaulted during her fertile
period was given large doses of estrogen twice for 1 day
to interrupt a possible pregnancy.
• If fertilization had occurred, what do you think
would be the mechanism of action of this hormone?
• What do lay people call this type of medical
treatment? Is this what the media refer to as the
“abortion pill?” If not, explain the method of action
of the hormone treatment.
• How early can a pregnancy be detected?
CASE 3-3
A 23-year-old woman consulted her physician about
severe right lower abdominal pain. She said that she had
missed two menstrual periods. A diagnosis of ectopic
pregnancy was made.
• What techniques might be used to enable this
diagnosis to be made?
• What is the most likely site of the extrauterine
gestation?
• How do you think the physician would likely treat
the condition?
CASE 3-4
A 30-year-old woman had an appendectomy toward the
end of her menstrual cycle; 81/2 months later, she had a
child with a congenital anomaly of the brain.
• Could the surgery have produced this child’s
congenital anomaly?
• What is the basis for your views?
CASE 3-5
A 42-year-old woman finally became pregnant after
many years of trying to conceive. She was concerned
about the development of her baby.
References and Suggested Reading
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extraembryonic mesoderm in experimental animals: relevance to
chorionic mosaicism in humans. Am J Med Genet 46:542, 1993.
Bukulmez O, Arici A: Luteal phase defect: Myth or reality. Obstet
Gynecol Clin N Am 31:727. 2004.
Cadkin AV, McAlpin J: The decidua-chorionic sac: A reliable
sonographic indicator of intrauterine pregnancy prior to detection of
a fetal pole. J Ultrasound Med 3:539, 1984.
Coulam CB, Faulk WP, McIntyre JA: Spontaneous and recurrent
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Dickey RP, Gasser R, Olar TT, et al: Relationship of initial chorionic
sac diameter to abortion and abortus karyotype based on new growth
curves for the 16 to 49 post-ovulation day. Hum Reprod 9:559, 1994.
Enders AC, King BF: Formation and differentiation of extraembryonic
mesoderm in the rhesus monkey. Am J Anat 181:327, 1988.
Hertig AT, Rock J: Two human ova of the pre-villous stage, having a
development age of about seven and nine days respectively. Contrib
Embryol Carnegie Inst 31:65, 1945.
Hertig AT, Rock J: Two human ova of the pre-villous stage, having a
developmental age of about eight and nine days, respectively. Contrib
Embryol Carnegie Inst 33:169, 1949.
Hertig AT, Rock J, Adams EC: A description of 34 human ova within
the first seventeen days of development. Am J Anat 98:435, 1956.
Hertig AT, Rock J, Adams EC, Menkin MC: Thirty-four fertilized
human ova, good, bad, and indifferent, recovered from 210 women of
known fertility. Pediatrics 23:202, 1959.
Kodaman PH, Taylor HS: Hormonal regulation of implantation. Obstet
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Lessey BA: The role of the endometrium during embryo implantation.
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Levine D: Ectopic pregnancy. In Callen PW (ed): Ultrasonography in
Obstetrics and Gynecology, 4th ed. Philadelphia, WB Saunders,
2000.
Lindsay DJ, Lovett IS, Lyons EA, et al: Endovaginal sonography: Yolk
sac diameter and shape as a predictor of pregnancy outcome in the
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Lipscomb GH: Ectopic pregnancy. In Copeland LJ, Jarrell JF (eds):
Textbook of Gynecology, 4th ed. Philadelphia, WB Saunders, 2000.
Luckett WP: The origin of extraembryonic mesoderm in the early
human and rhesus monkey embryos. Anat Rec 169:369, 1971.
Luckett WP: Origin and differentiation of the yolk sac and
extraembryonic mesoderm in presomite human and rhesus monkey
embryos. Am J Anat 152:59, 1978.
Nogales FF (ed): The Human Yolk Sac and Yolk Sac Tumors. New
York, Springer-Verlag, 1993.
Sen C, Yayla M: Chromosomal abnormalities of the embryo. In Kurjak
A, Chervenak FA, Carrera JM (eds): The Embryo as a Patient. New
York, Parthenon Publishing Group, 2001.
Streeter GL: Developmental horizons in human embryos. Description
of age group XI, 13 to 20 somites, and age group XII, 21 to 29
somites. Contrib Embryol Carnegie Inst 30:211, 1942.